Many common and pervasive human diseases are genetically complex; that is, they result from the interaction of multiple genetic, developmental, and environmental factors. Even single gene mutation diseases are frequently modulated in onset, severity, and progression by modifier genes. The long-term objective of this project, the Special Mouse Strains Resource (SMSR), is to maintain, distribute, and provide information for genetic tools for analyzing complex traits. The resources in the SMSR currently include six Recombinant Inbred (Rl) and two Chromosomal Substitution (CS) strain sets of mice that are valuable tools to improve the efficiency of identifying genes in mouse models of human multigenic diseases. These sets of mouse strains provide a perpetual resource for phenotyping with cumulative genotyping. A major new initiative in this application is a proposal to enhance the power of the C57BL/6J- Chr#A/NaJ Chromosomal Substitution (consomic) set by developing a set of germ line competent, embryonic stem cell lines from the individual strains to be used for testing candidate genes in co-isogenic strain backgrounds, cellular phenotyping, and in-vitro modeling of quantitative traits. The Specific Aims of the grant are to: 1) maintain strains of mice currently included in the SMSR as live colonies and to distribute these mice to investigators; 2) enhance the value of the SMSR strains by making, and distributing, ES cell lines for each of the C57BL/6J-Chr#A/NaJ consomic strains; and 3) provide complete and accurate information for SMSR strains that is easily accessible to the scientific community. Identification of genes responsible for complex diseases in mouse models often predicts the location of human disease genes, based on the conserved regions of mouse and human genomes; consequently, these resources significantly contribute to the resolution of complex genetic diseases in humans.